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NDVI data are crucial for agricultural and environmental research. The Fengyun-3 (FY-3) series satellites are recognized as primary sources for retrieving NDVI products on a global scale. To apply FY-3 NDVI data for long-term studies, such as climate change, this study conducted a thorough evaluation to detect the potentials of the FY-3B and FY-3D satellites for generating a long time series NDVI dataset. For this purpose, the spatiotemporal consistency between the FY-3B and FY-3D satellites was evaluated, and their performances were compared. Then, a grey relational analysis (GRA) method was applied to detect the factors influencing the consistency among the different satellites, and a gradient boosting regression (GBR) model was constructed to create a long-term FY-3 NDVI product. The results indicate an overall high consistency between the FY-3B and FY-3D NDVIs, suggesting that they could be used as complementary datasets for generating a long-term NDVI dataset. The correlations between the FY-3D NDVI and the MODIS NDVI, as well as the leaf area index (LAI) measurements, were both higher than those of FY-3B, which indicates a better performance of FY-3D in retrieving NDVI data. The grey correlation degrees between the NDVI differences and four parameters, which were land cover (LC), DEM, latitude (LAT) and longitude (LON), were calculated, revealing that the LC was the most related to the NDVI differences. Finally, a GBR model with FY-3B NDVI, LC, DEM, LAT and LON as the input variables and FY-3D NDVI as the target variable was established and achieved a robust performance. The R values between the GBR-estimated NDVI and FY-3D NDVI reached 0.947, 0.867 and 0.829 in the training, testing and validation datasets, respectively, indicating the feasibility of the established model for generating long time series NDVI data by combining data from the FY-3B and FY-3D satellites. [ABSTRACT FROM AUTHOR]

The passive microwave land surface emissivity (MLSE) plays a crucial role in retrieving various land surface and atmospheric parameters and in Numerical Weather Prediction models. The retrieval accuracy of MLSE depends on many factors, including the consistency of the input data acquisition time. The FengYun-3D (FY-3D) polar-orbiting meteorological satellite, equipped with passive microwave and infrared bands, offers time-consistent data crucial for MLSE retrieval. This study proposes a physics-based MLSE retrieval algorithm using all the input data from the FY-3D satellite. Based on the retrieved MLSE, the spatial distribution of the MLSE is closely correlated with the land cover types and topography. Lower emissivities prevailed over barren or sparsely vegetated regions, river basins, and coastal areas. Higher emissivities dominated densely vegetated regions and mountainous areas. Moderate emissivities dominated grasslands and croplands. Lower-frequency channels showed larger emissivity differences with different polarizations than those of higher-frequency channels in barren or sparsely vegetated regions. The MLSE across densely vegetated land areas, mountainous areas, and deserts showed small seasonal variations. However, woody savannas, grasslands, croplands, and seasonal snow-covered areas showed noticeable seasonal variations. For most land cover types, the differences between vertically and horizontally polarized emissivities remained relatively constant across seasons. However, certain grasslands in eastern Inner Mongolia and southern Mongolia showed clear seasonal variations. It is very difficult to verify the MLSE on a large scale. Consequently, the possible error sources in the retrieved MLSE were analyzed, including the brightness temperature errors (correlation coefficient ranging from 0.92 to 0.99) and the retrieved land surface temperature errors (Root Mean Square Error was 3.34 K and relation coefficient was 0.958). [ABSTRACT FROM AUTHOR]

For many years, the Advanced Very High-Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments have been widely used to monitor the condition of surface vegetation. Since the polar-orbiting satellite provides limited daily samples on surface, a completed spatial coverage of land vegetation is often relied on over multiple days of observations. In this study, observations from the Japanese geostationary satellite imager Advanced Himawari Imagers (AHI) are used to derive the surface vegetation index. The AHI reflectance at visible and near-infrared bands are first corrected to the surface reflectance by using the 6S radiative transfer model. The AHI surface reflectance from various viewing angles and solar geometry is further normalized to form an angular-independent reflectance by using a BRDF model. Finally, the surface vegetation index is calculated and synthesized from the daytime AHI data. It is found that the high-frequency AHI observations can significantly reduce the impact of clouds on compositing land NDVI and require a shorter time for a complete coverage of surface conditions. Also, a single NDVI image from AHI exhibits spatial distribution similar to that from 16 days of MODIS data. [ABSTRACT FROM AUTHOR]

Abstract: The urokinase plasminogen activator system, which is a serine protease family include urokinase-type plasminogen activator (uPA), the uPA receptor and plasminogen activator inhibitors (PAIs). uPA catalyzes the transformation of plasminogen to its active form plasmin, which is able to degrade the extracellular matrix (ECM) and basement membranes, directly or indirectly through activating pro-matrix metalloproteinases (pro-MMPs), promoting cancer cell metastasis and invasion. Both uPA and PAI-1 are poor prognosis markers in primary breast cancer. Evidence has been presented that the uPA system facilitates breast cancer metastasis by several different mechanisms, such as the Ras-ERK pathway and p38 MAPK pathway. This review focuses on uPA system, summarizes their biological effects, highlights the molecular mechanism and pathway, and discusses the role of uPA system in the prevention and treatment of human breast cancers. [Copyright &y& Elsevier]

Curcumin can induce p53-independent apoptosis. However, the underlying mechanism remains to be defined. Here, we show that curcumin-induced apoptosis in a panel of tumor cells with mutant p53. Curcumin rapidly induced activation of the mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK). Inhibition of JNK (with SP600125) or Erk1/2 (with U0126) partially prevented curcumin-induced cell death in the cells. Similarly, expression of dominant negative c-Jun or downregulation of Erk1/2 in part attenuated curcumin-induced cell death. It appears that curcumin-induced activation of MAPKs and apoptosis was due to induction of reactive oxygen species (ROS), as pretreatment with N-acetyl-L-cysteine, a ROS scavenger, blocked these events. Furthermore, we found that curcumin-induced activation of MAPK pathways was related to inhibition of the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5). Overexpression of PP2A or PP5 partially prevented curcumin-induced activation of JNK and Erk1/2 phosphorylation as well as cell death. The results suggest that curcumin induction of ROS activates MAPKs, at least partially by inhibiting PP2A and PP5, thereby leading to p53-independent apoptosis in tumor cells. [ABSTRACT FROM AUTHOR]

Influence of microsphere--crosslinked ratio on the performance of crosslinked polymer microsphere was studied by dynamic light scattering experiments, scanning e-electron microscopy experiments, nuclear pore membrane filtrating experiments and core flooding experiments. The experimental results show that swelling microspheres sizes are different because of different hydration crosslinked ratio; the smaller the crosslinked ratio becomes, the looser microspheres structure is, the larger swelling multiple is. With he decrease of crosslinked ratio, the soft degree of microsphere increased, and the deformability of microsphere enhanced. The nuclear pore membrane filtrating experimental results show that the microspheres with moderate size and better deformability have better blocking ability. The core flooding experiments results further show that the microsphere with better deformability can easier access to the deep reservoir and occur closure. The field application test shows hat the polymer microsphere system can increase oil production and reduce water. [ABSTRACT FROM AUTHOR]

Poly-surfactant to fit the characteristics of the fracture-cave type carbonate reservoirs in Tahe oilfield is selected. The experimental results showed that the oil-water interfacial tension reaches 10-2 mN/m when the poly-surfactant is in the lower concentration of 0.035%. The interracial tension can be lower than 10-2 mN/m at high temperature and high salt reservoir conditions. By using poly- surfactant, the crude oil viscosity can be reduced to 94% above, and the interfacial tension maintained within 10-2 mN/m after heated for 30 days. The simulated crack experiment showed that salted water cannot displace oil when the gap less than 4.0mm, but the poly-surfactant water can displace oil substantially when the gap was 1.16mm. The combination of suture holes simulation experiments showed that the greater the crack width is, the more the simulated oil out of the hole is. [ABSTRACT FROM AUTHOR]

Abstract: Gross primary production (GPP) is a parameter of significant importance for carbon cycle and climate change research. Remote sensing combined with other climate and meteorological data offers a convenient tool for large scale GPP estimation. This paper presents a study of GPP estimation using three methods with in situ measurements of canopy reflectance, LAI, and the photosynthetically active radiation (PAR). First, because LAI is considered as an indicator of the factor of absorbed PAR (f APAR), it provides reasonable estimates of GPP for all types of wheat with coefficient of determination R 2 of 0.7353. The second method uses four kinds of vegetation indices (VIs) to estimate GPP because these indices are suggested to be reliable candidates in the estimation of light use efficiency (LUE). Good determination coefficients were acquired in estimating GPP with R 2 ranging from the lowest of 0.7604 for NDVI to the highest of 0.8505 for EVI. A new method was proposed for the estimation of GPP following the Monteith logic, which considering GPP as a product of VI×VI×PAR. Results indicated that this method can provide the best estimates of GPP as determination coefficient R 2 increased largely compared to the other two methods. EVI×EVI×PAR was demonstrated to be the most suitable for the estimation of GPP with the highest R 2 of 0.9207, which was about 10% larger as compared to GPP estimated from the single EVI. These results will be helpful for the development of new models of GPP estimation with all remote sensing inputs. [Copyright &y& Elsevier]

Estimation of chlorophyll content and the leaf area index (LAI) using remote sensing technology is of particular use in precision agriculture. Wavelengths at the red edge of the vegetation spectrum (705 and 750 nm) were selected to test vegetation indices (VIs) using spaceborne hyperspectral Hyperion data for the estimation of chlorophyll content and LAI in different canopy structures. Thirty sites were selected for the ground data collection. The results show that chlorophyll content and LAI can be successfully estimated by VIs derived from Hyperion data with a root mean square error (RMSE) of 7.20-10.49 μg cm-2 for chlorophyll content and 0.55-0.77 m2 m-2 for LAI. The special index derived from three bands provided the best estimation of the chlorophyll content (RMSE of 7.19 μg cm-2 for the Modified Chlorophyll Absorption Ratio Index/Optimized Soil-Adjusted Vegetation Index (MCARI/OSAVI705)) and LAI (RMSE of 0.55 m2 m-2 for a second form of the MCARI (MCARI2705)). These results demonstrate the possibilities for analysing the variation in chlorophyll content and LAI using hyperspectral Hyperion data with bands from the red edge of the vegetation spectrum. [ABSTRACT FROM AUTHOR]

Abstract: Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity that limits its clinical use by generation of reactive oxygen species (ROS) and apoptosis. Protection or alleviation of doxorubicin cardiotoxicity can be achieved by administration of natural phenolic compounds via activating endogenous defense systems and antiapoptosis. Naringenin-7-O-glucoside (NARG), isolated from Dracocephalum rupestre Hance, has been demonstrated to protect against cardiomyocyte apoptosis. In the present study, we investigated the effects of NARG on endogenous antioxidant enzymes against doxorubicin toxicity and the potential role of extracellular signal-regulated kinase (ERK) in regulation of NARG-induced Nrf2-dependent gene expression in H9c2 cardiomyocytes. The mRNA expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutamate-cysteine ligase catalytic subunit (GCLC) was upregulated by NARG as detected by RT-PCR. NARG (10, 20, and 40μM) pretreatment increased NAD (P) H: quinone oxidoreductase (NQO1), ERK, and Nrf2 protein levels in cardiomyocytes as detected by Western blotting. These results suggest that NARG could prevent cardiomyocytes from doxorubicin-induced toxicity by induction of endogenous antioxidant enzymes via phosphorylation of ERK1/2 and nuclear translocation of Nrf2. [Copyright &y& Elsevier]

Abstract: Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-O-glucoside (10, 20, and 40 μM) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, naringenin-7-O-glucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin. [Copyright &y& Elsevier]

In recent years, the areas damaged by the East Asia migratory locust plagues (Locusta migratoria manilensis) have enlarged geographically in China. Some outbreaks in parts of the Dagang region, in the east coast of China, have caused drastic reductions in the yield of agricultural reeds and have created a severe threat to local and regional agriculture. Currently, the monitoring system for this species depends on field observations conducted by sparsely distributed observing stations established in the 1950s. This observation network was. in the past, successfully operated to identify major locust outbreaks. However, due lo the expansion of infestation areas and the increase of locust density, spatial information technology was needed to establish a satellite sensor-based monitoring system for the East Asia migratory locust plagues. This Letter outlines the preliminary experimental work conducted in 2001 for a feasibility study in establishing a sensor-based locust monitoring system. In this experiment, sample statistics of biomass and leaf area index (LAI) from the affected and non-affected areas by locusts were calculated, and the spectra of field reed samples from both areas were also evaluated together with synchronous Landsat Enhanced Thematic Mapper (ETM+) multi-spectral data. The study showed that satellite sensors may be used operationally to monitor locust damage. [ABSTRACT FROM AUTHOR]

Based on the meteorological data (2009–2018) acquired by high-density automatic meteorological stations in the central urban area (CUA) of Beijing, this study adopted an urban-rural ratio method to construct a qr to quantify the impact of urbanization on the spatial and temporal distribution of specific humidity (q). And the urban morphological parameters such as building height (BH), building density (BD), floor area ratio (FAR), sky view factor (SVF), and land surface parameters including vegetation coverage (VC) and impervious coverage (IC) with 500-m spatial resolution in CUA were calculated, and furthermore, the relationships between the six spatial layout parameters and another indicator, urban heat island (UHI) intensity, and qr were studied. The results show that q of CUA is 81~114% of that of the suburbs, and the urban dry island (UDI) effect and urban wet island (UWI) effect coexist throughout the year. The maximum UDI occurs during autumn daytime and the maximum UWI appears at night in winter. The UDI effect is prone to occur in areas with VC < 11%, IC >85%, BH > 15 m, and BD > 24%, while the UWI effect is more likely to appear in areas with VC > 35% and FAR < 0.3. The contributions of the six urbanization parameters to the spatial change of qr in different time periods are 6.2 to 33.5%, and VC is the largest (33.5%), followed by BD (31.9%) and SVF (29.9%), and the main factor affecting the annual average qr is BD with the contribution of 18.9%. Compared with the urbanization parameters, the UHI is more important and the contribution to the change of q can be up to 35.7%. The results show that these spatial layout parameters are not sufficient to explain the main change in q, and more other parameters need to be considered. [ABSTRACT FROM AUTHOR]

Black carbon (BC) has importance regarding aerosol composition, radiative balance, and human exposure. This study adopted a backward-trajectory approach to quantify the origins of BC from anthropogenic emissions (B C An) and open biomass burning (B C BB) transported to Xishuangbanna in 2017. Haze months, between haze and clean months, and clean months in Xishuangbanna were defined according to daily PM 2.5 concentrations of >75, 35–75, and <35 µg/m3, respectively. Results showed that the transport efficiency density (TED) of BC transported to Xishuangbanna was controlled by the prevailing winds in different seasons. The yearly contributions to the effective emission intensity of B C An and B C BB transported to Xishuangbanna were 52% and 48%, respectively. However, when haze occurred in Xishuangbanna, the average B C An and B C BB contributions were 23% and 77%, respectively. This suggests that open biomass burning (BB) becomes the dominant source in haze months. Myanmar, India, and Laos were the dominant source regions of BC transported to Xishuangbanna during haze months, accounting for 59%, 18%, and 13% of the total, respectively. Furthermore, India was identified as the most important source regions of B C An transported to Xishuangbanna in haze months, accounting for 14%. The two countries making the greatest contributions to B C BB transported to Xishuangbanna were Myanmar and Laos in haze months, accounting for 55% and 13%, respectively. BC emissions from Xishuangbanna had minimal effects on the results of the present study. It is suggested that open BB in Myanmar and Laos, and anthropogenic emissions in India were responsible for poor air quality in Xishuangbanna. [Display omitted] [ABSTRACT FROM AUTHOR]

Apoptosis occurs frequently in myocardial infarction, oxidative stress injury, and ischemia/reperfusion injury, and plays a pivotal role in the development of heart diseases. Inhibition of apoptosis alone does not necessarily lead to meaningful rescue in terms of either cardiomyocyte survival or function. Activation of the PI3K/Akt signaling pathway induced by insulin not only inhibits cardiomyocyte apoptosis but also substantially preserves and even improves regional and overall cardiac function. Insulin can protect cardiomyocytes from apoptosis by regulating a number of signaling molecules, such as eNOS, FOXOs, Bad, GSK-3β, mTOR, NDRG2, and Nrf2, through activating PI3K and Akt. This review focuses on the protective mechanisms and targets of insulin identified in the prevention and treatment of myocardial injury. [ABSTRACT FROM AUTHOR]

• New AC and ocean IOP algorithms developed for YF-3D MERSI-II sensor. • First ocean color products from FY-3D MERSI-II sensor are demonstrated. • Algorithm based on machine learning method driven by coupled atmosphere-ocean RT simulations. • Completely resolved negative water-leaving signal issue plagues heritage algorithms. • Algorithm is globally applicable, reliable, robust and efficient. Heritage atmospheric correction (AC) and ocean inherent optical property (IOP) retrieval algorithms, such as those implemented in NASA's SeaDAS platform, often produce questionable results in complex environments, such as in turbid coastal and inland waters and for heavy aerosol loadings. We present new AC and ocean IOP retrieval algorithms for the Medium Resolution Spectral Imager - II (MERSI-II) onboard the FengYun-3D satellite that solve these problems. The algorithm development is based on extensive radiative transfer simulations for a coupled atmosphere-ocean system in conjunction with machine learning techniques (i.e. multi-layer neural networks) to retrieve ocean color products from MERSI-II sensor data. The final ocean color products include spectral remote sensing reflectances (R rs (λ) values), chlorophyll_a concentration (CHL), and IOPs, i.e. absorption by phytoplankton (a ph (λ)), absorption by detritus and gelbstoff (a dg (λ)), and particulate backscattering (b bp (λ)). Spectral aerosol optical depths (AODs) and cloud mask results are also provided. The new machine learning based algorithms are first tested using independent synthetic datasets and show very good performance. The average percentage error (APE) is less than 7% for the R rs retrievals and less than 5.2% for the AOD retrievals with a 1% uncertainty added to the TOA reflectances. The ocean color products retrieved from MERSI-II sensor data are validated against AERONET-OC field measurements and show good quality. For Rrs retrievals, the APE is around 30% for blue and red bands and 22% for green band. For AOD retrievals, the APE is also around 23% - 30%, and for CHL retrievals, the APE is around 32%. The ocean color products retrieved from MERSI-II sensor data are also cross-validated with the corresponding ones retrieved from Aqua/MODIS data using both NASA SeaDAS package and our machine learning based OC-SMART algorithms. The results show that these machine learning algorithms completely resolve the negative R rs (λ) issue that persists in heritage AC algorithms and significantly improve the quality of retrieved ocean color products, especially in coastal regions. The histograms of the retrieved R rs , CHL, and ocean IOP products also show good agreement between MERSI-II and Aqua/MODIS ocean color retrievals. [ABSTRACT FROM AUTHOR]

Abstract Tumor hypoxia is a well-known microenvironmental factor that causes cancer progression and resistance to cancer treatment. Proline hydroxylases (PHDs), a small protein family, belong to an evolutionarily conserved superfamily of dioxygenases, considered the central regulator of the molecular hypoxia response. Prolyl-4-hydroxylase 2 (PHD2), one member of PHDs family, regulates the stability of the hypoxia-inducible factor-1 alpha (HIF-1α) in response to oxygen availability. During hypoxia, the inhibition of PHD2 permits the accumulation of HIF-1α, allowing the cellular adaptation to oxygen limitation, causing activation of numerous genes, which enhances the angiogenesis, metastasis and invasiveness. Accurate regulation of oxygen homeostasis is essential, and which implies PHD2 may have a regulatory role in the pathogenesis of cancer. Although ample evidence exists for a positive correlation between HIFs and tumor formation, metastasis and poor prognosis, the function of the PHD2 in carcinogenesis is less well understood. Despite their original role as the oxygen sensors of the cell and many of the its functions are clearly conveyed through the HIF system, PHD2 is currently known to display HIF-independent and hydroxylase-independent functions in cancer cells and stroma in the control of different cellular pathways. In this review, we summarize the recent advances in the structure, regulation and functions of PHD2 in cancer microenvironment. Graphical abstract Image 1 Highlights • PHD2 mediates hydroxylation of HIF-1α. • PHD2 is regulated at transcriptional, proteasomal and protein-interactions levels. • PHD2 displays pro and antitumoral effects depending on the cellular context. • PHD2 has very dynamic subcellular trafficking during cancer progression. • PHD2 is associated with different signaling pathways such as Akt, PP2A and EGFR. [ABSTRACT FROM AUTHOR]

Abstract Highly expressed Zinc-finger E-box binding protein 1 (ZEB1) is significantly associated with the malignancy of various cancers. Signal transduction and activation of ZEB1 play important roles in cancer transformation and epithelial-mesenchymal transition (EMT). Emerging evidence suggests that ZEB1 drives the induction of EMT with activation of stem cell traits, immune evasion and epigenetic reprogramming. As an ideal target for EMT research, ZEB1 has been extensively studied for decades. However, the link between ZEB1 and epigenetic regulation of EMT has only recently been discovered. ZEB1 facilitates the epigenetic silencing of E-cadherin by recruiting multiple chromatin enzymes of E-cadherin promoter, such as histone deacetylases (HDACs), DNA methyltransferase (DNMT) and ubiquitin ligase. Destruction of the connection between ZEB1 and these chromatin-modifying enzymes may represent an efficient for treating cancer. In this review, we outlined the biological function of ZEB1 in tumorigenic progression and epigenetic modifications and elucidate its transcriptional network, which is a suitable potential target for the design of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Abstract Non-small cell lung cancer (NSCLC) is known as highly metastatic disease because it is difficult to diagnose at early stage. More than 60% of NSCLC patients' overexpress receptor tyrosine kinase (RTK) such as EGFR that has been proved to display resistance to receptor tyrosine kinase inhibitor (TKI) through PI3K signaling, while single PI3K inhibitors increase RTK expression as feedback. So, to select the proper targeted agent or target an assortment of molecular subsets, such as EGFR mutations for different subgroups of patients with NSCLC is urgent. Compound BENC-511, a potent PI3K inhibitor, had effects on inhibiting cancer cell survival and delaying tumor growth, but the effects and mechanisms on cancer metastasis are not clear. Methods of Scratch assay, Transwell system, experimental metastasis mice models, plasmid transfection, quantitative real-time PCR and Western blot were used. Results showed that BENC-511 could significantly inhibit lung cancer cells invasion and metastasis both in vitro and in vivo. And it not only inhibited PI3K/Akt signal pathway, but also directly suppressed phosphorylation of EGFR and nuclear translocation of β-catenin. Moreover, our study firstly reported BENC-511 seemed more sensitive to NSCLC cells that highly expressed Zinc-finger E-box binding protein 1 (ZEB1), one of the epithelial-mesenchymal transition (EMT) inducer, and knockdown of ZEB1 could improve the effects of this compound. These findings suggested that BENC-511 should be a promising lead molecule for anti-metastasis therapy by targeting β-catenin/ZEB1 regulatory loop and serve as a therapeutic agent to inhibit metastasis of NSCLC. Graphical abstract Image 1 Highlights • BENC-511 could inhibit migration and invasion of A549 cells in vitro. • BENC-511 could inhibit lung metastasis of melanoma cells B16BL6 in vivo. • BENC-511 could inhibit lung tumor growth in vivo. • BENC-511 could suppress MMP-9 via PI3K/Akt/mTOR/β-catenin pathway. • BENC-511 could inhibit EGFR and β-catenin/ZEB1 regulatory loop. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most serious malignant tumors that harm to women’s health. Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels, which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Prior antiangiogenic therapy just focused on vascular endothelial cells and did not significantly affect VM. DMBT, 6, 6′-bis (2, 3-dimethoxybenzoyl)-a, a- D -trehalose, has shown to have multiple anti-tumor invasion and metastasis activities; however the exact mechanism is not thoroughly elucidated. In this study, we examined key molecular mechanisms underlying VM by using breast cancer cells MDA-MB-231 and MCF-7. We found that following the hypoxia treatment, the cells were easily to form VM networks and DMBT could inhibit VM formation of both MDA-MB-231 and MCF-7 cells in hypoxic condition. When tumor cells exposed to hypoxia environment, the expression of VM related proteins such as HIF-1α, VE-cadherin, MMP-9, Cdc42, and EGFR, p-Akt, p-mTOR were increased but decreased when exposed to hypoxia medium with DMBT. In MDA-MB-231 cells, DMBT inhibit hypoxia-induced VM by suppress HIF-1α/VE-cadherin/MMPs signaling pathway and in MCF-7 cells, DMBT had little effect on HIF-1α or VE-cadherin but could inhibit cell autophagy to suppress VM formation. These results suggested that DMBT could serve as a therapeutic agent to inhibit VM formation in human breast cancer. [ABSTRACT FROM AUTHOR]

Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice. Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting. JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model. The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease. [Display omitted] • Jian Pi Qing Gan Yin (JPQGY) ameliorated high-fat diet-induced NAFLD in mice. • Network pharmacology analysis revealed JPQGY regulating 10 NAFLD-associated lipid metabolism pathways. • JPQGY regulated the AMPK/PPARα pathway. • JPQGY inhibited the LXRα/Srebp1/Nf-κb pathway in the livers of NAFLD mice. [ABSTRACT FROM AUTHOR]

Tumors require a blood supply for survival, growth, and metastasis. It is widely accepted that the development of the tumor microcirculation compartment need the production of new blood vessels (angiogenesis). Vasculogenic mimicry (VM) is an alternative type of blood supplement independent of endothelial vessels which refers to the formation of tumor cell-lined vessels and is associated with tumor invasion, metastasis and poor cancer patient prognosis. Although a variety of proteins and microenvironmental factors are known to contribute to VM, the mechanisms underlying its formation remain unclear. The induction of VM seems to be related to hypoxia, which may promote the plastic, transendothelial phenotype of tumor cells capable of VM. Here, with regard to the above aspects, we review the advanced research on VM including molecular mechanisms and its clinical significance; and explore the development of VM-related strategies which are being utilized for anticancer treatment. [ABSTRACT FROM AUTHOR]

Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients. Development of efficient anti-invasive agents is an important research challenge. 6,6′-bis (2,3-dimethoxybenzoyl)-a, a- d -trehalose (DMBT), one of brartemicin analogs, was found to be the most potent anti-invasive agent, but the underlying mechanisms are poorly understood. Our current study was to explore the effects of DMBT on invasion and metastasis in B16BL6 cells. Antiproliferation assay and trypan blue exclusion assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found in B16BL6 cells. Wound healing demonstrated that DMBT could inhibit cell migration compared with the normal group. Transwell experiments showed that DMBT could significantly inhibit invasion to the reconstituted basement membrane ( P < 0.01). We examined the effects of lung metastasis produced by highly metastatic B16BL6 melanoma cells by using experimental metastasis models and BLI analysis. DMBT could significantly suppress lung metastasis in mice. Results from immunohistochemical staining, Western blotting and real-time PCR indicated that the chemopreventive effect of DMBT was attributed to the inhibition of the VEGF and MMP-9 through Akt/GSK-3β/β-catenin and Akt/mTOR signaling pathways. These results suggested that DMBT could be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit cancer cell invasion and metastasis. [ABSTRACT FROM AUTHOR]

Phosphoglycerate kinase 1 (PGK1) is an essential enzyme that catalyzes adenosine 5′-triphosphate (ATP) production in aerobic glycolysis. In addition to regulating cell metabolism, PGK1 is involved in multiple biological activities, including angiogenesis, mediated autophagy starting, binding of plasminogen, the DNA replication and repair, the proliferation and metastasis of tumor cells, cell invasion (a part of the flagellar axoneme and viral replication and it occurs mainly in protists), and is also associated with resistance to chemotherapy and prognosis of cancer patients. In this review, we focus on the basic functions of PGK1 and the relationship between PGK1 and different diseases, indicating that PGK1 has a broad application prospect to find a potential biomarker for tumor prognosis and an effective inhibitor. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. In order to obtain more potent inhibitors, a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion. Among the synthetic analogs tested, DMBT, 6,6′-bis (2,3-dimethoxybenzoyl)-a,a-d-trehalose, was found to be the most potent anti-invasive agent. But the effects of DMBT on breast cancer cells were not known. In this study, the effects of DMBT on invasion and metastasis in MDA-MB-231 cells were investigated. MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found. DMBT could inhibit invasion, migration and tube formation of HUVECs. Gelatin zymography showed that DMBT inhibited secretion and activity of MMP-9. Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt. These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGFand MMP-9, resulting from the inhibition of Akt pathway. DMBT might be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis. [Copyright &y& Elsevier]

Abstract: Cadmium (Cd), a highly toxic environmental pollutant, induces neurodegenerative diseases. Recently we have demonstrated that Cd induces neuronal apoptosis in part through activation of the mammalian target of rapamycin (mTOR) pathway. However, the underlying mechanism is unknown. Here we show that Cd induces the generation of reactive oxygen species (ROS) by upregulating the expression of NADPH oxidase 2 and its regulatory proteins (p22phox, p67phox, p40phox, p47phox, and Rac1) in PC12 and SH-SY5Y cells. Cd induction of ROS contributed to the activation of mTOR signaling, as pretreatment with N-acetyl-l-cysteine (NAC), a ROS scavenger, prevented this event. Further studies reveal that Cd induction of ROS increased phosphorylation of the type I insulin-like growth factor receptor (IGFR) β subunit, which was abrogated by NAC. Wortmannin, a phosphoinositide 3′-kinase (PI3K) inhibitor, partially attenuated Cd-induced phosphorylation of Akt, p70 S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1, as well as apoptosis of the neuronal cells. In addition, overexpression of wild-type phosphatase and tensin homologue deleted on chromosome 10 (PTEN) or pretreatment with aminoimidazole carboxamide ribonucleotide, an AMP-activated protein kinase (AMPK) activator, partially prevented Cd-induced ROS and activation of the mTOR pathway, as well as cell death. The results indicate that Cd induction of ROS activates mTOR signaling, leading to neuronal cell death, in part by activating the positive regulators IGFR/PI3K and by inhibiting the negative regulators PTEN/AMPK. The findings suggest that inhibitors of PI3K and mTOR, activators of AMPK, or antioxidants may be exploited for the prevention of Cd-induced neurodegenerative diseases. [Copyright &y& Elsevier]

Abstract: The aim of this study was to design and characterize lectin-modified solid lipid nanoparticles (SLNs) containing insulin and to evaluate the potential of the lectin-modified colloidal carriers for oral administration of peptide and protein drugs. SLNs were prepared by three different methods. For comparison, some insulin-loaded SLNs were modified with wheat germ agglutinin-N-glutaryl-phosphatidylethanolamine (WGA-N-glut-PE). The particle size, zeta potential and entrapment efficiency of insulin-loaded SLNs were determined. Insulin-loaded SLNs prepared by an appropriate modification of the double dispersion method yielded the highest drug entrapment efficiency, which was more than 60%. In vivo experiments were carried out using insulin-loaded SLNs and WGA-modified SLNs prepared by this method. SLNs and WGA-modified SLNs protected insulin against degradation by digestive enzymes in vitro. The stabilizing effect of WGA-modified SLNs was greater than that observed in SLNs. After oral administration of insulin-loaded SLNs or WGA-modified SLNs to rats, the relative pharmacological bioavailabilities were 4.46% and 6.08%, and the relative bioavailabilities were 4.99% and 7.11%, respectively, in comparison to subcutaneous injection of insulin. These results demonstrated that SLNs and WGA-modified SLNs promoted the oral absorption of insulin. [Copyright &y& Elsevier]

• APHRODITE, CHIRPS, PERSIANN-CDR were evaluated over TP. • Performance of gridded products varied in precipitation occurrences and amount. • APHRODITE performed the best and with longest time span (>50 years). • PERSIANN-CDR outperformed CHIRPS in detecting rainfall occurrences. Long-term precipitation data play significant roles in hydrological applications and climate change studies. In this study three gridded precipitation products (Asian Precipitation-Highly Resolved Observational Data Integration Towards Evaluation of Water Resources, APHRODITE; Climate Hazards Group InfraRed Precipitation with Station data, CHIRPS; and Precipitation Estimation from Remotely sensed Information using Artificial Neural Networks-Climate Data Record, PERSIANN-CDR) with the spatial resolution of 0.25° were evaluated using rain gauge data at the daily, monthly and annual scales over the Tibetan Plateau and its surrounding areas (TP). R2, bias, RMSE and MAE were adopted to assess precipitation amount; indices including the probability of detection (POD), false alarm ratio (FAR), critical success index (CSI) and frequency bias index (FBI) were used to evaluate gridded products' ability to detect precipitation occurrences. We found that: (1) APHRODITE outperformed CHIRPS and PERSIANN-CDR against observations at the annual scale with the highest R2 (~0.93), the lowest MAE (~67 mm/year) and RMSE (~116 mm/year), and APHRODITE also showed better performance in distinguishing rain/no rain events with the highest POD (~0.9) and CSI (>0.6), the lowest FAR (~0.35), followed by PERSAINN-CDR and CHIRPS; (2) CHIRPS performed nearly to APHRODITE in precipitation amount with R2 around 0.8 while the lowest POD (<0.4) implied the shortage for CHIRPS in detecting rain/no rain conditions; (3) in spite of the lowest agreement with gauge measurements with the largest bias (~25%), PERSIANN-CDR had a relatively higher mean POD (>0.5), indicating that PERSIANN-CDR had better potential of detecting rainfall occurrences than CHIRPS but tended to overestimate precipitation; (4) generally, PERSIANN-CDR overestimated the precipitation greater than CHIRPS and APHRODITE data at monthly scale; and (5) the three products correlated well with each other in the interior, southern and eastern regions of TP but there were still some significant differences along the borders and surroundings of the TP by inter-comparisons. Finally, we recommended APHRODITE for climate change study for its high accuracy and long-time series, CHIRPS and PERSIANN-CDR could also be considered after correction. [ABSTRACT FROM AUTHOR]

• First exploration on downscaling IMERG at hourly scale in typhoon event. • Proposed a new downscaling strategy based on moving window technology. • Cloud properties from Himawari 8 introduced for downscaling IMERG. • Downscaled results outperformed the original IMERG data. Accurate gridded precipitation products with both finer tempo-spatial resolutions are critical for various scientific communities (e.g., hydrology, meteorology, climatology, and agriculture). Downscaling on coarse satellite-based rainfall estimates is an optimal approach to obtain such datasets. The Integrated Multi-satellitE Retrivals for Global Precipitation Measurement (GPM) (IMERG) data provides the "best" satellite-based precipitation estimates at half-hourly/0.1° scales, while its spatial resolution is still coarse for certain hydrometeorology research. To acquire hourly downscaled precipitation estimates based on IMERG, there are two great challenges: (1) limited rainfall-related environmental variables (0.01°×0.01°, hourly) used to downscale the IMERG data; and (2) far few rainfall pixels used for regressing traditional relationships between precipitation and environmental variables. In this case, most traditional or commonly-used regression/empirical models and the state-of-art machine learning algorithms are not suitable to cater these requirements. Therefore, we proposed a new strategy to obtain hourly downscaled precipitation estimates based on IMERG called Geographically Moving Window Weight Disaggregation Analysis (GMWWDA). Additionally, we explored multiple cloud properties, including cloud effective radius (CER), cloud top height (CTH), cloud top temperature (CTT) and cloud optical thickness (COT), as covariates to downscale IMERG using GMWWDA method, and concluded as follows: (1) the downscaled results (0.01° × 0.01°, hourly) based on the above mentioned cloud properties outperformed the original IMERG data; (2) the downscaled results based on CER performed better than those based on CTH, CTT and COT, respectively; (3) the accuracy of satellite-based precipitation products pose significant effects on those of the downscaled results. This study provides a great potential solution for generating satellite-based precipitation dataset with finer spatio-temporal resolutions. [ABSTRACT FROM AUTHOR]

Diabetes mellitus-related cardiomyopathy (DMCMP) has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause such as coronary artery disease or hypertension. Mechanisms underlying DMCMP have not been fully elucidated. In this study, the roles of protein phosphatase 2A/nuclear factor NF-E2-related factor 2 (PP2A/Nrf2) in experimental DMCMP induced by high glucose were studied in vitro and in vivo. The results showed that high glucose could induce experimental DMCMP and increase ROS generation, increase the expression and nuclear translocation of Nrf2, down-regulate the expression of PI3K/Akt/mTOR and up-regulate the expression of ERK, and activate the autophagy of cardiomyocytes. The activity or expression of PP2A in DMCMP increased. PP2A could up-regulate the expression of Nrf2 and promote cardiomyocytes autophagy and apoptosis. Inhibition of PP2A could reduce the expression of Nrf2 and inhibit the autophagy and apoptosis of cardiomyocytes. The results suggested that hyperglycemic-induced experimental DMCMP may be related to up-regulating the expression of Nrf2 through PP2A/Nrf2 pathway. These results will be helpful to elucidate the pathogenesis and mechanism of DMCMP and find targets for the development of new drugs to prevent or treat DMCMP. Unlabelled Image • High glucose could induce DCM by increase ROS generation and Nrf2 expression. • High glucose could enhance autophagy by regulating ERK and PI3K/Akt/mTOR. • PP2A could regulate autophagy and apoptosis by regulating Nrf2, caspase-3, and Bcl-2. • Inhibition ROS generation in the same time could reverse the results. [ABSTRACT FROM AUTHOR]